Porins are members of a distinguishable family of water filled channels in the outer membrane of gram negative bacteria which are inherently stable to harsh conditions of pH, temperature, detergents, and proteases. Comprised of transmembrane a-sheets, long extracellular loop domains and periplasmic-faced turns, these molecules associate and are only functional as trimers. We have been studying a number of porins isolated from pathogenic neisserial strains (primarily meningococcal) in order to establish a relationship between functional and structural features, and to characterize the overall thermodynamic stability as well as specific factors accounting for such unique features. Meningococcal porins are gene products of PorA and PorB genes which express PorA (class1) and Por B (either class 2 or class 3), respectively. Our preliminary studies have revealed that PorA class 1 and PorB class 2 exhibit comparable stability to chemical and thermal denaturation. Class 3 protein not only presents a lower free energy of unfolding in Gdn[unreadable]HCl denaturation studies, but also exhibits the presence of a low temperature transition (~ 65 C) in addition to a major transition at 90 C, the latter observed for the other two neisserial porins. These results correlate with the SDS-sensitivity of PorB class 3 protein which may be correlated with weaker interactions between the putative loop regions involved in the trimeric assembly. The transmembrane domains appear to exhibit comparable stability for the three porins and probably do not undergo complete unfolding upon thermal denaturation since a significant content of secondary structure is retained at 95 C. Studies are currently in progress to delineate the mechanisms of these differences and to characterize the thermal stability of hybrid mutants comprised of lower and higher stability PorA and PorB domains.